Abstract

The rate of divergence between species, and the level diversity within a species, are expected to depend on the rate of mutation. Here we investigate the relationship between divergence, diversity and the rate of mutation across the human genome at scales of 1MB and 100KB using >40,000 de novo mutations (DNM). We show that there is significant variation in the rate of DNM across the human genome, but that the variation is modest. Different types of mutation show similar levels of variation and appear to vary in concert. Regressing the rate of DNM against a range of genomic features suggests that nucleosome occupancy is the most important correlate, but that GC content, recombination rate, replication time and various histone methylation signals also correlate significantly. In total the model explains ~75% of the explainable variance. As expected the rate of divergence between species and the level of diversity within humans is correlated to the rate of DNM. However, the correlations are weaker than if all the variation in divergence was due to variation in the mutation rate. We provide evidence that this is due the effect of biased gene conversion on the probability that a mutation will become fixed. Finally, we show that the correlation between divergence and DNM density declines as increasingly divergent species are considered. Our results have important implications for the use of divergence and diversity data to study variation in the mutation rate.

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